Cancer-on-a-chip research into metastases – ICT & health

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Research into new cancer treatments focuses mainly on attacking and destroying rapidly dividing cancer cells. The greatest danger of not getting this disease under control, however, lies in the metastases when the cancer cells spread to other organs. Knowledge about this development of cancer, called metastasis, is still very limited, making treatment or prevention difficult. This should be improved with the help of the cancer-on-a-chip research by PhD student Sleeboom.

Understanding metastasis

Metastasis takes place on a very small scale and is therefore difficult to follow. Only one or a few cancer cells need to detach from the tumor, enter the bloodstream and settle elsewhere. This also complicates research into the effect of metastasis.

“What makes the understanding of metastases even more difficult is that cancer cells do not spread by themselves, but are influenced in all kinds of ways by their environment,” says Jelle Sleeboom. The environment of the primary tumor is also referred to as the tumor microenvironment. This micro environment often has a low oxygen content. The cancer cells are controlled by the gradient from low to high oxygen concentration around the tumor.

Cancer cells are also affected by the extracellular matrix. This is a fibrous network of proteins around cells that provides structure and strength to tissues. In tumors, the firmness and fiber structure of this matrix changes, which can affect the spread of cancer.

Cancer-on-a-chip

During his research on metastasis, Jelle developed methods to study the effect of oxygen and the extracellular matrix outside the human body. Based on microfluidics, the science of manipulating fluids on a small scale, he developed tiny computer chips that he could make resemble the tumor microenvironment. Cancer cells are grown on these chips in small chambers and fluid channels.

“This makes the cancer cells think they are inside a person. The big difference is that these chips provide control over the microenvironment of the tumor, so that the effect of the different factors on cancer cells can be systematically investigated, ”says Jelle. During his research, Jelle first developed a chip that could control the oxygen gradient. The cancer cells could be followed with this chip.

He then showed that a certain type of breast cancer cell is attracted to lower oxygen concentrations. A surprising finding, given that cancer cells were expected to look for more oxygen. “This discovery could potentially teach us more about behavior in humans. We then further developed this technique, so that we can see whether we see the same behavior when the cells are in an extracellular matrix, ”says Jelle.

The use of computer chips in research into (organ) diseases is a development that has been used successfully for several years. At the end of last year, a researcher from the University of Twente succeeded in developing a heart-on-a-chip. At the beginning of this year, Mimetas presented its first Assay Ready organ-on-a-chip product line. According to the manufacturer, this is an important step forward in the pursuit of making organ-on-a-chip technology available to everyone.

Further development

Sleeboom has recently worked mainly on the development of a more realistic extracellular matrix than has been used in the research so far. A matrix that looks like the situation in and around the primary tumor before the cancer cells separate and spread. Cancer cells that secrete actually have to pass through a thin membrane. That phase is called invasion.

Sleeboom developed a method to surround cancer cells with such a membrane before the cells are introduced into the extracellular matrix. This allowed him to monitor the invasion and further investigate this process, for example by varying the composition of the matrix. “The techniques we have developed contribute to the further development of cancer-on-a-chip and will hopefully lead to a better understanding or even methods to prevent cancer metastasis in the future,” says Sleeboom.

Jelle Sleeboom will be awarded a PhD for his cancer-on-a-chip research on 29 September.





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